Use of sodium-hydrogen ion antiporter 1 inhibitors e.g. N-(4,5-bis-methanesulfonyl-2-methyl-2-methyl-benzoyl)-guanidine, used at doses causing only partial inhibition, e.g. for treating arrhythmia or angina

摘要

Use of sodium-hydrogen ion (Na+/H+) antiporter 1 (NHE1) inhibitors (I) is claimed in the production of medicaments for treating or preventing diseases, where NHE1 is only partially inhibited : An independent claim is included for pharmaceutical compositions (A) containing (I), where NHE1 is only partially inhibited by administration of (A). ACTIVITY : Antiarrhythmic; Antianginal; Cardiant; Cerebroprotective; Vasotropic; Antiarteriosclerotic; Antidiabetic; Cytostatic; Antiinflammatory; Hypotensive. In tests in rats with myocardial infarction surgically induced by ligation, N-(4,5-bis-methanesulfonyl-2-methyl-2-methyl-benzoyl)-guanidine (Ia) was administered orally (at 200 ppm in feed), for 3 months starting 2 weeks after ligation, to give a plasma level of 500 ng/ml (causing 75% inhibition of NHE1) initially and 238 ng/ml (causing 60% inhibition of NHE1) after 3 months. Cardiac hypertrophy was completely prevented. MECHANISM OF ACTION : NHE1 inhibitor. In a test, (Ia) exhibited an IC50 value of 455 nM for inhibition of human platelet NHE1.